Citations

Abstract Lesson Learned Panitumumab plus irinotecan is not active for the treatment of esophageal adenocarcinoma. Background Esophageal adenocarcinoma (EAC) is a lethal cancer with increasing incidence. Panitumumab (Pa) is a fully humanized IgG2 monoclonal antibody against human EGFR. Cetuximab (Cx) combined with irinotecan (Ir) is active for second-line treatment of colorectal cancer. This phase II study was designed to evaluate Pa plus Ir as second-line therapy for advanced EAC. Methods The primary endpoint was response rate (RR). Patients with one prior treatment were given Pa 9 mg/m2 on day 1 and Ir 125 mg/m2 on days 1 and 8 of each 21-day cycle. Inclusion criteria were confirmed EAC, measurable disease, no prior Ir or Pa, performance status <2, and normal organ function. Results Twenty-four patients were enrolled; 18 were eligible and evaluable. These patients were all white, with a median age of 62.5 years (range, 33–79 years), and included 15 men and 3 women. The median number of cycles was 3.5. The most common grade 1–2 adverse events were fatigue, diarrhea, anemia, leukopenia, and hypoalbuminemia. Grade 3–4 adverse events included hematologic, gastrointestinal, electrolyte, rash, fatigue, and weight loss. The median follow-up was 7.2 months (range, 2.3–14 months). There were no complete remissions. The partial response rate was 6% (1/18; 95% confidence interval [CI], 0.01–0.26). The clinical benefit (partial response [PR] plus stable disease [SD]) rate was 50%. The median overall survival was 7.2 months (95% CI, 4.1–8.9) with an 11.1% 1-year survival rate. The median progression-free survival was 2.9 months (95% CI, 1.6–5.3). Conclusion Irinotecan and panitumumab as second-line treatment for advanced EAC are not active.

AbstractIntroductionSince the introduction of wearable head‐up displays, there has been much interest in the surgical community adapting this technology into routine surgical practice.MethodsWe used the keywords augmented reality OR wearable device OR head‐up display AND surgery using PubMed, EBSCO, IEEE and SCOPUS databases. After exclusions, 74 published articles that evaluated the utility of wearable head‐up displays in surgical settings were included in our review.ResultsAcross all studies, the most common use of head‐up displays was in cases of live streaming from surgical microscopes, navigation, monitoring of vital signs, and display of preoperative images. The most commonly used head‐up display was Google Glass. Head‐up displays enhanced surgeons' operating experience; common disadvantages include limited battery life, display size and discomfort.ConclusionsDue to ergonomic issues with dual‐screen devices, augmented reality devices with the capacity to overlay images onto the surgical field will be key features of next‐generation surgical head‐up displays.

Purpose: Anterior cervical discectomy and fusion has a low but well-established profile of adverse events. The goal of this study was to gauge surgeon opinion regarding the frequency and acceptability of these events. Methods: A 2-page survey was distributed to attendees at the 2015 Cervical Spine Research Society (CSRS) meeting. Respondents were asked to categorize 18 anterior cervical discectomy and fusion–related adverse events as either: “common and acceptable,” “uncommon and acceptable,” “uncommon and sometimes acceptable,” or “uncommon and unacceptable.” Results were compiled to generate the relative frequency of these responses for each complication. Responses for each complication event were also compared between respondents based on practice location (US vs. non-US), primary specialty (orthopedics vs. neurosurgery) and years in practice. Results: Of 150 surveys distributed, 115 responses were received (76.7% response rate), with the majority of respondents found to be US-based (71.3%) orthopedic surgeons (82.6%). Wrong level surgery, esophageal injury, retained drain, and spinal cord injury were considered by most to be unacceptable and uncommon complications. Dysphagia and adjacent segment disease occurred most often, but were deemed acceptable complications. Although surgeon experience and primary specialty had little impact on responses, practice location was found to significantly influence responses for 12 of 18 complications, with non-US surgeons found to categorize events more toward the uncommon and unacceptable end of the spectrum as compared with US surgeons. Conclusions: These results serve to aid communication and transparency within the field of spine surgery, and will help to inform future quality improvement and best practice initiatives.

Abstract Checkpoint inhibitors targeted at programmed cell death-1 receptor (PD-1) and its ligand (PD-L1) can result in significant benefit to a small proportion of patients with cancer, including those with tumors of the stomach and gastroesophageal junction. These drugs are now approved for several solid tumors, including the recent accelerated approval of pembrolizumab for gastroesophageal adenocarcinomas in the third-line setting and beyond based on the KEYNOTE-059 phase II trial. Data are lacking on the efficacy of chemotherapy after progression on PD-1 blockade in metastatic gastroesophageal adenocarcinoma. This report describes the exceptional response of two patients who received ramucirumab plus paclitaxel after progressive disease on pembrolizumab. This early clinical observation suggests that the sequence of administration of PD-1 blockade and chemotherapy may be important in this disease.

Abstract Kallikrein-related peptidase 6 (Klk6) is the most abundant serine proteinase in the adult central nervous system (CNS), yet we know little regarding its physiological roles or mechanisms of action. Levels of Klk6 in the extracellular environment are dynamically regulated in CNS injury and disease positioning this secreted enzyme to affect cell behavior by potential receptor dependent and independent mechanisms. Here we show that recombinant Klk6 evokes increases in intracellular Ca2+ in primary astrocyte monolayer cultures through activation of proteinase activated receptor 1 (PAR1). In addition, Klk6 promoted a condensation of astrocyte cortical actin leading to an elongated stellate shape and multicellular aggregation in a manner that was dependent on the presence of either PAR1 or PAR2. Klk6-evoked changes in astrocyte shape were accompanied by translocation of β-catenin from the plasma membrane to the cytoplasm. These data are exciting because they demonstrate that Klk6 can influence astrocyte plasticity through receptor-dependent mechanisms. Furthermore, this study expands our understanding of the mechanisms by which kallikreins can contribute to neural homeostasis and remodeling and point to both PAR1 and PAR2 as new therapeutic targets to modulate astrocyte form and function.

Abstract Although neurogastroenterology and motility ( NGM ) disorders are some of the most frequent disorders encountered by practicing gastroenterologists, a structured competency‐based training curriculum developed by NGM experts is lacking. The American Neurogastroenterology and Motility Society ( ANMS ) and the European Society of Neurogastroenterology and Motility ( ESNM ) jointly evaluated the components of NGM training in North America and Europe. Eleven training domains were identified within NGM , consisting of functional gastrointestinal disorders, visceral hypersensitivity and pain pathways, motor disorders within anatomic areas (esophagus, stomach, small bowel and colon, anorectum), mucosal disorders (gastro‐esophageal reflux disease, other mucosal disorders), consequences of systemic disease, consequences of therapy (surgery, endoscopic intervention, medications, other therapy), and transition of pediatric patients into adult practice. A 3‐tiered training curriculum covering these domains is proposed here and endorsed by all NGM societies. Tier 1 NGM knowledge and training is expected of all gastroenterology trainees and practicing gastroenterologists. Tier 2 knowledge and training is appropriate for trainees who anticipate NGM disorder management and NGM function test interpretation being an important part of their careers, which may require competency assessment and credentialing of test interpretation skills. Tier 3 knowledge and training is undertaken by trainees interested in a dedicated NGM career and may be restricted to specific domains within the broad NGM field. The joint ANMS and ESNM task force anticipates that the NGM curriculum will streamline NGM training in North America and Europe and will lead to better identification of centers of excellence where Tier 2 and Tier 3 training can be accomplished.

Abstract In some cases, laparoscopic cholecystectomy (LC) may be difficult to perform in patients with acute cholecystitis (AC) with severe inflammation and fibrosis. The Tokyo Guidelines 2018 (TG18) expand the indications for LC under difficult conditions for each level of severity of AC. As a result of expanding the indications for LC to treat AC, it is absolutely necessary to avoid any increase in bile duct injury (BDI), particularly vasculo‐biliary injury (VBI), which is known to occur at a certain rate in LC. Since the Tokyo Guidelines 2013 (TG13), an attempt has been made to assess intraoperative findings as objective indicators of surgical difficulty; based on expert consensus on these difficulty indicators, bail‐out procedures (including conversion to open cholecystectomy) have been indicated for cases in which LC for AC is difficult to perform. A bail‐out procedure should be chosen if, when the Calot's triangle is appropriately retracted and used as a landmark, a critical view of safety (CVS) cannot be achieved because of the presence of nondissectable scarring or severe fibrosis. We propose standardized safe steps for LC to treat AC. To achieve a CVS, it is vital to dissect at a location above (on the ventral side of) the imaginary line connecting the base of the left medial section (Segment 4) and the roof of Rouvière's sulcus and to fulfill the three criteria of CVS before dividing any structures. Achieving a CVS prevents the misidentification of the cystic duct and the common bile duct, which are most commonly confused. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47 . Related clinical questions and references are also included.